Reorganization of human cortical maps caused by inherited photoreceptor abnormalities

Abstract

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization.

fMRI of the rod scotoma elucidates cortical rod pathways and implications for lesion measurements

“…It is important to note that none of these studies can measure the same neuron at multiple time points, but rather, they must sample from active neurons in similar locations, resulting in potential sampling biases that further complicate their interpretations (2,27). Similar conflicting measurements have been seen in human patients with bilateral foveal lesions from age-related macular degeneration, with some fMRI studies claiming extensive recovery within the V1 SPZ, whereas again, others showed no evidence for reorganization (7,18,35,(43)(44)(45).…”

“…Third, the scotoma arises because of the central fovea's complete lack and surrounding paucity of rod photoreceptors, allowing for a very close comparison with retinal lesions in animal models (5). Fourth, there is indirect evidence that the rod contributions to cortical activity are very similar to those of the cones, allowing for comparisons of changes in the properties of the cortical neurons overlapping the scotomas arising from either scotopic conditions or direct retinal lesions (6,7,13,14). Fifth, the rod scotoma is completely reversible on return to photopic conditions, allowing for the measurement of ectopic cortical responses caused by short-term cortical adaptation without contamination from long-term reorganization, such as that seen in the relatively permanent developmental foveal scotomas of rod monochromats (7).…”

“…This roughly circular rodfree zone covers a radius of ∼0.6-0.8°of visual angle about the fixation point (diameter = ∼1.25-1.7°) (4,5). Under scotopic conditions, a scotoma arises from these foveal, rod-free zones, because no photoreceptors are stimulated within these regions (6,7). Perceptual and fMRI estimates of the rod scotoma range from ∼1°to 2°of visual angle in radius because of the rod-sparse region surrounding the foveola and individual variability (6)(7)(8)(9).…”

“…First, the scotoma exists in all normal human subjects under scotopic conditions (5,7). Second, the scotoma is located in the central fovea, which has large swaths of early visual cortex devoted to its analysis (10)(11)(12).…”

Colour vision deficiency

“…It remains unclear as to what stage of development rescue would need to be instituted in order to result in improved vision in humans, as rod monochromacy has been shown to result in alterations to inner retinal structure, 67 alterations in the photoreceptor mosaic, 68 and in reorganisation of the visual cortex. 69 It is likely that these changes alone would have an impact on visual function: even if successful targeting of cone photoreceptors with wild-type achromatopsia genes can be achieved via viral vectors, vision is unlikely to be returned to normal once such changes have occurred. A more recent study by Mancuso et al 70 has investigated the amelioration of red-green colour vision deficiency in an animal model of protanopia.…”